A periodontal tissue regeneration strategy via biphasic release of zeolitic imidazolate framework-8 and FK506 using a uniaxial electrospun Janus nanofiber

Guided tissue regeneration (GTR) strategy is an effective approach to repair periodontal defect by using GTR membranes. However, the commercial GTR membranes still have limitations in periodontal tissue regeneration owing...

Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique

Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.

Biphasic Drug Release from Rolled-Up Gelatin Capsules with a Cylindrical Cavity

Biphasic drug delivery systems are used for quick release of a specific amount of drug for immediate amelioration of a patient’s state, followed by sustained release, to avoid repeated administration. This type of delivery is often necessary for pain management and the treatment of many pathologies, such as migraines, hypertension, and insomnia. In this work, we propose a novel architecture of a biphasic release media that does not need the rapidly disintegrating layer and that allows for easily setting the sustained release rate. A drug-containing capsule is made by rolling up a thermally crosslinked gelatin strip on which drug reservoirs are formed by casting. The quick-release reservoir (QRR) is placed at the strip’s extremity, from which the rolling starts, while the sustained-release reservoir (SRR) is formed in the middle part of the strip. The strip is rolled around a cylinder that is a few millimeters wide, which is removed after rolling. The roll is stabilized by transglutaminase-catalyzed crosslinking of the consecutive shells. A biphasic release is successfully demonstrated with the use of model fluorescent drugs for single-dye and double-dye systems in phosphate-buffered saline (PBS) solution with pH = 7.4. In vitro, the drug from the QRR, placed at the walls of the cavity of the roll, is released immediately upon the capsule’s contact with the PBS solution. The drug from the SRR, embedded between the roll’s layers, diffuses steadily, with the lag time defined by the radial position of the reservoir.

Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets

Novel calcium phosphate-based starter pellets were used to develop a biphasic-release multiple-unit pellet system (MUPS) with diclofenac sodium as a model drug in the form of hard gelatin capsules. For comparative purposes, corresponding formulations based on the inert cores made of microcrystalline cellulose, sucrose and isomalt were prepared. The developed system consisted of two types of drug-layered pellets attaining different release patterns: delayed-release (enteric-coated) and extended-release. Dissolution characteristics were examined using both compendial and biorelevant methods, which reflected fed and fasting conditions. The results were collated with an equivalent commercial product but prepared with the direct pelletization technique.

XT-type DNA Hydrogels Loaded with VEGF and NGF Promote Peripheral Nerve Regeneration via Biphasic Release Profile

Peripheral nerve injury (PNI) remains an unresolved challenge in the medicine area. With the development of biomaterial science and tissue engineering, a variety of nerve conduits were widely applied in...

Development of Asialoglycoprotein Receptor-Targeted Nanoparticles for Selective Delivery of Gemcitabine to Hepatocellular Carcinoma

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1–G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug (p < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p < 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma.

Physico-Chemical and Biological Evaluation of PLCL/SF Nanofibers Loaded with Oregano Essential Oil

Essential oils are complex volatile compounds, extracted from specific plant species, with promising therapeutic potentials. However, their volatile nature presents a major hindrance in using them as therapeutic agents. In the current study, we successfully encapsulated oregano essential oil (OEO) into Poly (l-lactic acid-co-e-caprolactone) /Silk Fibroin (PLCL/SF) polymers through electrospinning. The nanofibrous membrane (NF) was fabricated and characterized for various physico-chemical and biological attributions. Homogenous and bead free morphology was confirmed by scanning electron microscopy (SEM). Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the successful loading of OEO and its physical interaction with the blend of PLCL/SF. Moreover, thermogravimetric analysis (TGA) also confirmed the successful loading and thermostability of the OEO. Although a significant change was noted in tensile strength due to the loading of OEO, the mechanical behaviour still falls into the acceptable ranges required for skin tissue engineering. Similarly, fabricated material was evaluated for its biological significance. Liquid chromatography-mass spectrometry (LC-MS) was employed to determine the release behaviour of OEO from electrospun membranes. LC-MS data, noted for 48 h, confirmed the biphasic release of OEO. Furthermore, NF membranes have shown strong antioxidant and anti-tumor activities. This material is promising and can be implanted to avoid the recurrence of the tumor after its surgical removal.